Green tea compound could be gateway towards new cancer drugs

February 2021 Medical Research Willem van Altena

Could green tea hold the key to a novel approach to cancer medicine? An antioxidant found in green tea may increase levels of a natural anti-cancer protein. Published recently in Nature Communications, a study of the direct interaction between the protein p53 and the green tea compound epigallocatechin gallate (EGCG) suggests a new target for cancer drug discovery.

The discovery was made at the Rensselaer Polytechnic Institute in Troy, in upstate New York, USA. According to Chunyu Wang, corresponding author and a professor of biological sciences, both p53 and EGCG molecules are extremely interesting. “Mutations in p53 are found in over 50% of human cancer, while EGCG is the major anti-oxidant in green tea, a popular beverage worldwide. Now we find that there is a previously unknown, direct interaction between the two, which points to a new path for developing anti-cancer drugs. Our work helps to explain how EGCG is able to boost p53’s anti-cancer activity, opening the door to developing drugs with EGCG-like compounds.”

Cell death

Wang describes the p53 protein as “arguably the most important protein in human cancer.” It has several well-known anti-cancer functions, including halting cell growth to allow for DNA repair, activating DNA repair, and initiating programmed cell death (apoptosis) if DNA damage cannot be repaired. One end of the protein, known as the N-terminal domain, has a flexible shape, and therefore, can potentially serve several functions depending on its interaction with multiple molecules.

The chemical compound EGCG is a natural antioxidant, which means it helps to undo the near constant damage caused during oxygen metabolism. Found in abundance in green tea, EGCG is also packaged as an herbal supplement.

Important interaction

Wang’s team found that the interaction between EGCG and p53 preserves the protein against degradation. Typically, after being produced within the body, p53 is quickly degraded when the N-terminal domain interacts with a protein called MDM2. This regular cycle of production and degradation holds p53 levels at a low constant. “Both EGCG and MDM2 bind at the same place on p53, the N-terminal domain, so EGCG competes with MDM2,” says professor Wang. “When EGCG binds with p53, the protein is not being degraded through MDM2, so the level of p53 will increase with the direct interaction with EGCG, and that means there is more p53 for anti-cancer function. This is a very important interaction.”

Reference

Zhao, J., Blayney, A., Liu, X. et al. EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction. Nat Commun 12, 986 (2021). https://doi.org/10.1038/s41467-021-21258-5

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